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1.
Bone marrow mesenchymal stromal cells (MSCs) have shown therapeutic potential in the treatment of myocardial infarction patients. However, bone marrow requires invasive harvesting techniques. Therefore, the aim was to carry out a feasibility study of using autologous peripheral blood (PB) as a source for MSCs and platelet lysate (PL), a potential novel therapeutic intervention in acute ST elevation myocardial infarction (STEMI) patients. Autologous PL and MSCs were prepared from STEMI patient and healthy control blood. MSCs were analyzed by trilineage differentiation and flow cytometry. PB MSCs were isolated from 83% of patients (n = 6) but not from controls. The use of PL was feasible in the first passage but not in subsequent ones due to volume. To conclude, PB is a promising alternative to bone marrow. It negates the need for invasive harvesting techniques, and reduces hemorrhagic risk in this patient population routinely managed with anticoagulant and antiplatelet agents.  相似文献   

2.
Bone marrow aspirates (BMAs), owing to their innate osteogenic potential, are well-documented supplements to osteoconductive and/or osteoinductive materials. The calcaneal body provides foot and ankle surgeons a convenient harvest site with low morbidity and minimal cost. In the present study, we sought to identify and characterize multipotent mesenchymal stromal cells (MSCs) in BMAs harvested from the human calcaneal body. Ten healthy patients aged 18 to 65 years were enrolled in the present study. BMAs were harvested from the patients without any reported postoperative complications related to the harvest. Cells isolated from all the aspirates were adherent to culture plates and expressed positive MSC surface markers (CD105, CD90, and CD73) and a low level of negative MSC markers (CD34 and CD45). The cells maintained the ability to proliferate and differentiate into cells of mesenchymal lineages. The BMAs from the human calcaneal body offer a healthy source of multipotent MSCs.  相似文献   

3.
Many reports have shown that bone marrow–derived mesenchymal stem cells exhibit immunosuppressive effects in allogeneic transplantation. However, few reports have evaluated the immunosuppressive properties of adipose tissue–derived mesenchymal stem cells (ASCs) in vitro and in vivo. In this study, we investigated the immunosuppressive characteristics of ASCs, and investigated whether ASCs originating from donor rats prolong allotransplant survival in a rat hind limb allotransplantation model. T-cell proliferation stimulated by allogeneic stimuli or mitogen with or without ASCs originating from the donor was assessed in vitro. The effects of cellular contact or soluble factors on the inhibition of T-cell proliferation were also evaluated. In the in vivo study, cultured ASCs (1 × 105) that originated from the donor were injected into recipient animals intravenously immediately after operation, followed by 1 dose per day for 3 consecutive days post-transplantation. When immune rejection occurred, the survival time of allotransplants was determined and rejected tissue was histologically and immunochemically assessed for determining regulatory T-cell infiltration. ASCs inhibited the T-cell proliferation stimulated by alloantigen or mitogen in a dose-dependent manner, and recipient T cells proliferated less in animals treated with ASCs than in controls. Although ASCs were separated from T cells, ASCs persisted to elicit a suppressive effect. ASC culture supernatants did not inhibit T-cell proliferation; however, supernatants obtained from the mixed lymphocyte reaction in the presence of ASCs suppressed T-cell proliferation. ASCs prolonged allotransplant survival time, reduced inflammatory cell infiltration, and induced regulatory T cells. In conclusion, ASCs can exhibit in vitro immunosuppressive properties and prolong allotransplant survival time in a rat hind limb composite tissue allotransplantation model, possibly through the induction of regulatory T cells.  相似文献   

4.
The elucidation of the molecular mechanisms that govern the differentiation and proliferation of human adipose tissue‐derived mesenchymal stem cells (hASCs) could improve hASC‐based cell therapy. In this study, we examined the roles of microRNA (miRNA)‐196a on hASC proliferation and osteogenic differentiation. Lentiviral overexpression of miR‐196a decreased hASC proliferation and enhanced osteogenic differentiation, without affecting adipogenic differentiation. Overexpression of miR‐196a decreased the protein and mRNA levels of HOXC8, a predicted target of miR‐196a. HOXC8 expression was decreased during osteogenic differentiation of hASCs, and this decrease in HOXC8 expression was concomitant with an increase in the level of miR‐196a. In contrast, inhibition of miR‐196a with 2′‐O‐methyl‐antisense RNA increased the protein levels of HOXC8 in treated hASCs and was accompanied by increased proliferation and decreased osteogenic differentiation. The activity of a luciferase construct containing the miR‐196a target site from the HOXC8 3′UTR was lower in LV‐miR196a‐infected hASCs than in LV‐miLacZ‐infected cells. RNA interference‐mediated downregulation of HOXC8 in hASCs increased their proliferation and decreased their differentiation into osteogenic cells, without affecting their adipogenic differentiation. Our data indicate that miR‐196a plays a role in hASC osteogenic differentiation and proliferation, which may be mediated through its predicted target, HOXC8. This study provides us with a better knowledge of the molecular mechanisms that govern hASC differentiation and proliferation.  相似文献   

5.
6.
Although dogma predicts that under normal circumstances, potentially offensive autoreactive cells are silenced by mechanisms of immune tolerance, islet antigen–reactive B lymphocytes are known to play a crucial role in the development of autoimmunity in type 1 diabetes (T1D). Thus, participation of these cells in T1D may reflect escape from silencing mechanisms. Consistent with this concept, we found that in healthy subjects, high-affinity insulin-binding B cells occur exclusively in the anergic naive IgD+, IgM B-cell (BND) compartment. Antigen receptors expressed by these cells are polyreactive and have N-region additions, Vh usage, and charged complementarity-determining region 3 consistent with autoreactivity. Consistent with a potential early role in autoimmunity, these high-affinity insulin-binding B cells are absent from the anergic compartment of some first-degree relatives and all prediabetic and new-onset (<1 year) T1D patients tested, but return to normal levels in individuals diabetic for >1 year. Interestingly, these changes were correlated by transient loss of the entire BND compartment. These findings suggest that environmental events such as infection or injury may, by disrupting B-cell anergy, dispose individuals toward autoimmunity, the precise nature of which is specified by genetic risk factors, such as HLA alleles.  相似文献   

7.
对28例2型糖尿病行胃旁路手术治疗患者,进行健康指导、心理护理;术后重视血糖监测、饮食护理、并发症护理、保持胃管引流通畅,加强自理行为能力训练等围术期护理。结果28例患者术后血糖基本恢复正常,术后3周停止使用降糖药物(包括胰岛素)并不再限制饮食。11例术后随访1年,示糖尿病治愈。提示围术期护理干预在促进患者恢复方面起到积极作用。  相似文献   

8.
2型糖尿病行胃旁路手术患者的护理   总被引:3,自引:0,他引:3  
对28例2型糖尿病行胃旁路手术治疗患者,进行健康指导、心理护理;术后重视血糖监测、饮食护理、并发症护理、保持胃管引流通畅,加强自理行为能力训练等围术期护理.结果28例患者术后血糖基本恢复正常,术后3周停止使用降糖药物(包括胰岛素)并不再限制饮食.11例术后随访1年,示糖尿病治愈.提示围术期护理干预在促进患者恢复方面起到积极作用.  相似文献   

9.
目的:探讨2型糖尿病肾病(DN)患者血清、尿脂联素水平变化及与血浆可溶性血栓调节蛋白(sTM)的关系。方法:根据尿白蛋白排泄率(UAER)将82例2型糖尿病患者分成糖尿病正常白蛋白尿组(DM)、微量白蛋白尿组(DN1)和大量白蛋白尿组(DN2);应用酶联免疫吸附法(ELAISA)测定各组血清、尿中的脂联素,血浆sTM水平。结果:DN1组的血清脂联素水平高于DM组(P〈0.01),DN2组的血清脂联素水平高于DN1组(P〈0.01)。DN1组的尿脂联素水平高于DM尿组(P〈0.05),DN2的尿脂联素水平高于DN1组(P〈0.01)。DN1组的血浆sTM水平高于DM组(P〈0.01),DN2组的血浆sTM水平高于DM组(P〈0.01)。血清脂联素与尿脂联素、UAER、血浆sTM呈正相关(r=0.564,0.412,0.587,P〈0.01),与Ccr呈负相关(r=-0.362,P〈0.01);尿脂联素与Scr、UAER、血浆sTM呈正相关(r=0.292,0.748,0.775,P〈0.01),与Ccr(r=-0.379,P〈0.01)呈负相关。结论:2型DN患者血清、尿脂联素水平可能是反映DN早期内皮损害的重要生物标记物。  相似文献   

10.
There is a critical clinical need to develop therapies for nonhealing diabetic foot ulcers. Topically applied mesenchymal stromal cells (MSCs) provide a novel treatment to augment diabetic wound healing. A central pathological factor in nonhealing diabetic ulcers is an impaired blood supply. It was hypothesized that topically applied allogeneic MSCs would improve wound healing by augmenting angiogenesis. Allogeneic nondiabetic bone-marrow derived MSCs were seeded in a collagen scaffold. The cells were applied to a full-thickness cutaneous wound in the alloxan-induced diabetic rabbit ear ulcer model in a dose escalation fashion. Percentage wound closure and angiogenesis at 1 week was assessed using wound tracings and stereology, respectively. The topical application of 1,000,000 MSCs on a collagen scaffold demonstrated increased percentage wound closure when compared with lower doses. The collagen and collagen seeded with MSCs treatments result in increased angiogenesis when compared with untreated wounds. An improvement in wound healing as assessed by percentage wound closure was observed only at the highest cell dose. This cell-based therapy provides a novel therapeutic strategy for increasing wound closure and augmenting angiogenesis, which is a central pathophysiological deficit in the nonhealing diabetic foot ulcer.Diabetes is reaching epidemic proportions worldwide. Diabetic foot ulceration is the most frequent reason for hospitalization, and nonhealing ulceration may progress to amputation in spite of current standards of care. Nonhealing diabetic foot ulceration poses a major burden on individual patient health and healthcare budgets. Foot ulceration will affect 15–25% of people suffering from diabetes throughout their lives (1). Diabetes-related lower extremity amputation arises from pre-existing ulceration in 85% of cases (2). The high rate of progression from ulceration to amputation occurs despite standard care protocols. A central pathological factor in the treatment of nonhealing diabetic ulcers is impaired angiogenesis in the wound.There is a critical clinical need to develop novel treatments to improve healing of diabetic foot ulcers. Mesenchymal stromal cells (MSCs) provide a novel therapeutic treatment and have been shown to be beneficial in diabetic wound healing (3). The mechanisms underlying the beneficial effect of wound healing include paracrine secretion of growth factors and chemokines requisite for wound healing and the differentiation into keratinocytes and endothelial cells required for wound healing and angiogenesis. MSCs can be delivered in an allogeneic fashion and possess immunosuppressant and immunomodulatory properties (4).To date, there have been encouraging results in preclinical models of diabetic wound healing. Treatment with MSCs resulted in increased wound closure, new granulation tissue formation, and increased blood vessel formation and cellularity (58). In addition, 10 humans have received autologous MSCs, resulting in augmented wound healing. There is one report of an effect related to dose with autologous MSCs seeded in a fibrin spray (9). Nonetheless, there have been no studies using allogeneic human MSC transplantation in the setting of diabetic cutaneous ulceration. There is a paucity of data on effective dosing strategies in the literature. In this study, we report for the first time a dose-response evaluation of allogeneic transplantation of MSCs delivered through a collagen scaffold to an ulcer in a diabetic animal model.Previous research has shown that infusions of several cell types into the body rapidly undergo cell death (10). After intravenous delivery, MSCs are found at low or very low frequencies in target organs (11). The use of biomaterials in conjunction with stem cell therapy in vivo may ensure sustained viability and functionality of cells (10). Collagen supports angiogenesis (12). A biomaterial such as collagen allows targeted delivery and positioning of high numbers of cells at the wound site. It was hypothesized that topical application of a collagen scaffold seeded with allogeneic nondiabetic bone marrow–derived MSCs would support angiogenesis and augment cutaneous wound closure in a diabetic animal model of cutaneous ulceration. The therapeutic effect of collagen seeded MSC therapy in a preclinical model using wound tracings and stereology was investigated. This technique is a scientifically robust validated strategy to assess in vivo tissue responses to tissue-engineered constructs.  相似文献   

11.

Background

Fat mass and obesity-associated protein (FTO) gene expression is known to correlate with obesity. Our aim was to investigate the FTO gene expression in paired omental and subcutaneous human adipose tissues from morbid and obese patients. To understand the role of CD68-positive macrophages in adipose tissues, the correlation with adiposity parameters such as adipocyte diameter and adipocyte radius was also measured. Drug and adiposity correlations were also analyzed.

Methods

Paired omental and subcutaneous adipose tissue were excised during elective surgery from morbidly obese (n?=?9) and obese (n?=?5) patients. FTO expressions were determined by quantitative PCR. Tissue sections were analyzed for their CD68 protein expressions by immunuhistochemistry.

Results

Omental and subcutaneous adipose tissue FTO gene expression levels were not found to differ significantly among morbidly obese and obese study groups. Serum aspartate aminotransferase e and alanine transaminase levels were found to be in negative correlation with subcutaneous fat tissue FTO expression rate. Antidiabetic drug use was found to be in correlation with adiposity. Both subcutaneous and omental fat cell diameters were found to have correlation with antidiabetic drug use. Omental fat cell diameter was found to enlarge together with omental CD68 protein expression. Subcutaneous macrophage number decreased while omental fat cell radius increased. Omental macrophage number was found in correlation with subcutaneous macrophage number.

Conclusions

Antidiabetic therapy was found to increase adiposity in omental and subcutaneous fat. Further research is needed with larger samples to explore the exact role of FTO in obesity.  相似文献   

12.
13.
目的:分析2型糖尿病住院患者的糖尿病肾脏疾病(DKD)的发生率及危险因素,为临床糖尿病肾脏疾病的防治工作提供理论依据。方法:对2008年1月~2010年8月在上海交通大学附属第六人民医院内分泌代谢科住院的2型糖尿病患者测定血糖、肾功能、血脂谱、24h尿白蛋白等。应用简化肾脏病膳食改良试验(MDRD)公式计算肾小球滤过率(GFRMDRD)。所有患者均由眼科医生进行眼底摄片。按2007年美国肾脏病基金会(NKF)的糖尿病和慢性肾脏疾病的临床诊断治疗指南,将研究人群分为正常组(NCKD)、非糖尿病性肾脏疾病(NDRD)组及DKD组。结果:(1)共入选患者2225例,男1184例,女1041例;平均年龄为(60.5±11.7)岁。本研究人群中,DKD的发生率为15.4%,NDRD的发生率为18.5%。(2)DKD组患者的年龄、糖尿病病程、收缩压、血肌酐、总胆固醇(TC)、低密度胆固醇水平(LDL-C)、24h尿白蛋白量均显著高于NDRD组(P〈0.05)。(3)Logistic回归分析显示:糖尿病病程(OR=1.077,95%CI为1.059~1.096,P〈0.01)、收缩压(OR=1.039,95%CI为1.032~1.047,P〈0.01)、糖化血红蛋白(OR=1.092,95%CI为1.032~1.156,P〈0.01)、TC(OR=1.171,95%CI为1.050~1.306,P〈0.01)、HDL-C(OR=0.558,95%CI为0.369~0.844,P〈0.01)是DKD发生的独立危险因素。结论:为有效地延缓2型糖尿病肾脏病变的发生及发展,临床工作中要严格控制血压、血糖、血脂。  相似文献   

14.
目的:探讨胰岛素强化治疗对2型糖尿病患者胆道术后的临床疗效。方法:72例胆道术后合并2型糖尿病患者随机分为强化治疗组和对照组各36例。强化治疗组给予强化胰岛素治疗,使血糖控制在4.4~6.1mmol/L;对照组给予常规胰岛素治疗,使血糖控制在10.0~11.1mmol/L。比较两组空腹血糖(FBG)、炎性指标及预后等。结果:强化治疗组FBG、体温、WBC明显低于对照组,抗生素使用天数、院内感染发生率、重症监护天数及术后并发症明显少于对照组,但低血糖发生率显著高于对照组,差异有统计学意义(P〈0.05)。结论:糖尿病患者胆道术后强化胰岛素治疗,可降低炎性反应,并减少抗生素用量及重症监护天数,降低术后并发症,但低血糖发生率较高。  相似文献   

15.
《Transplantation proceedings》2013,45(6):2141-2146
BackgroundDiabetes mellitus (DM) is the most prevalent cause of kidney failure. Some concerns have been raised about the kidney transplantation (KT) results in diabetic patients. Therefore, we compared outcomes between diabetic and non-diabetic KT patients.MethodsWe included all KT performed in type 2 diabetic patients in our center from July 1983 to December 2009 with graft survivals beyond 3 months. Nondiabetic controls were individually matched with diabetic patients with respect to gender, age, year of transplantation, number of donor HLA mismatches, and dialysis vintage. The two groups were compared concerning patient and graft survivals, delayed graft function (DGF), and prevalence of acute rejection episodes (ARE).ResultsThe 62 diabetic and 62 nondiabetic patients had a mean follow-up after KT of 102 ± 64 months. Diabetic patients and controls were similar for the matched variables. Death censored graft survivals of diabetics versus nondiabetics were 70% and 83% at 5 years and 54% and 71% at 10 years, respectively (P = .13). Patient survivals at 5 and 10 years were 69% and 50% for diabetic versus 96% and 84% for nondiabetic patients, respectively (P < .001). The prevalence of ARE and DGF did not differ (chi-squared test, P = .12). Multivariate Cox's proportional hazards analysis revealed DM (hazard ratio [HR] 7.72; P = .001) and viral hepatitis (HR = 4.18; P = .02) to correlate with reduced patient survival.ConclusionSurvival of diabetic patients after KT was reduced but death-censored graft outcomes were similar compared with matched nondiabetic patients. Concerns about graft survival should not prevent KT for diabetic patients with kidney failure.  相似文献   

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目的:研究银杏叶提取物(EGB)对2型糖尿病大鼠睾丸间质细胞雄激素合成的影响。方法:雄性SD大鼠30只,随机均分成3组:正常对照组、2型糖尿病组、EGB治疗组。用光镜和透射电镜观察EGB对2型糖尿病大鼠睾丸的形态学改变;ELISA法检测血清LH、T水平;半定量RT-PCR检测睾丸间质细胞类固醇激素合成急性调节蛋白(StAR)、细胞色素P450侧链裂解酶(P450scc)、细胞色素P45017a-羟化酶(P450c17)、3β-羟基类固醇脱氢酶Ⅰ型(3β-HSD1)、17β-羟基类固醇脱氢酶Ⅲ型(17β-HSD3)的mRNA水平。结果:糖尿病组光镜下睾丸间质细胞较正常对照组缩小;透射电镜下见到间质细胞核固缩,胞质内内质网减少。糖尿病组血清LH及T水平显著低于正常对照组(P<0.05);睾丸组织P450scc的mRNA水平显著低于正常对照组(P<0.01),StAR、17β-HSD3及3β-HSD1的mRNA水平也明显低于正常对照组(P<0.05),P450c17基因表达呈下降趋势(P>0.05);EGB治疗12周与糖尿病组比较睾丸组织病理改变较轻,血清LH、T含量升高(P<0.05),StAR、P450scc的mRNA水平升高(P<0.05),P450c17、17β-HSD3及3β-HSD1的mRNA水平呈上升趋势(P>0.05)。结论:EGB能减轻糖尿病大鼠睾丸损害并使2型糖尿病大鼠睾丸间质细胞合成和分泌T能力增强。  相似文献   

18.
目的:探讨影响初发2型糖尿病(T2DM)患者国际勃起功能指数-5(IIEF-5)评分的相关因素。方法:调查149例初发T2DM患者的IIEF-5评分与年龄、体重指数(BM I)、空腹血糖(FPG)、口服葡萄糖耐量实验(OGTT)中2 h血糖(2hPG)、空腹血胰岛素(INS)、空腹C肽、糖化血红蛋白(GHbA1c)、血清睾酮(T)、雌二醇(E2)、T/E2、血清一氧化氮(NO)、红细胞醛糖还原酶(AR)、吸烟、酗酒、伴发疾病(包括高血压、高脂血症、高尿酸血症、心脏疾病、肝脏疾病等)、其他慢性并发症(糖尿病神经病变、糖尿病视网膜病变、糖尿病肾病等)、药物使用(包括β受体阻滞剂、钙通道阻滞剂、血管紧张素转换酶抑制剂及利尿剂等可影响阴茎勃起功能的药物)的关系。结果:吸烟组、患有并发症组、伴发疾病组、应用药物治疗组IIEF-5评分明显低于对照组(P<0.05),饮酒组与不饮酒组的IIEF-5评分比较差异无显著性(P>0.05)。年龄、BM I、FPG、2hFPG、INS、GHBA1C、AR与IIEF-5评分具有显著性负相关关系(P<0.05);NO与IIEF-5评分具有显著性正相关关系(P<0.05),T、E2、T/E2与IIEF-5评分无相关关系(P>0.05)。结论:多种因素影响初发T2DM患者的IIEF-5评分。  相似文献   

19.
Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-β-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 ± 7.3 years, with a mean BMI of 30.8 ± 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.  相似文献   

20.
Circulating angiogenic cells (CACs) are vascular‐committed bone marrow‐derived cells that are dysfunctional in type 1 diabetes (T1D). Here we studied whether restoration of normoglycemia following islet transplantation is associated with better CAC function. We carried out a cross‐sectional study of 18 T1D patients, 14 insulin‐independent islet‐transplanted patients (ITA) and 14 healthy controls (C) evaluating in vivo and in vitro CACs viability and function. We found that the percentage of CACs in vivo did not differ among the three groups while the number of CAC colonies obtained from T1D, but not from ITA, was reduced compared to C (C = 7.3 ± 1.9, T1D = 0.9 ± 0.4 and ITA = 4.7 ± 1.9; p < 0.05 T1D vs. all). In vitro CAC migration/differentiation were similar, while in vivo an improved angiogenic ability of ITA compared to T1D was shown (capillary density: C = 93.5 ± 22.1, T1D = 19.2 ± 2.8 and ITA = 44.0 ± 10.5, p < 0.05 T1D vs. all). Increased apoptosis and lesser IL‐8 secretion were evident in CACs obtained from T1D compared to C and ITA. in vitro addition of anti‐hIL‐8 reduced the number of colonies obtained from C. Finally, T1D, but not ITA, had a lower endothelial‐dependent dilatation (EDD) compared with C. These data suggest that CAC function is altered in T1D and may be improved after islet transplantation.  相似文献   

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